一种有机镓化合物对小鼠的胚胎毒性和致畸性

本文报道２－二甲氨基环己氧基－二甲基镓的胚胎毒性和致畸性的试验结果。雌性小鼠在检出阴栓的当天定为妊娠ｄ０，于ｄ０～ｄ１５每天灌胃一次，剂量分１．５，３，６ｍｇ／ｋｇ三组，对照组给生理盐水，ｄ１７处死小鼠剖腹按常规方法检查胚胎毒性和致畸性。结果表明６ｍｇ／ｋｇ组２只母鼠中毒死亡，各染毒组母鼠体重增长迟缓。３和６ｍｇ／ｋｇ组出现明显胚胎毒性，早期吸收胎明显增加。染毒组活存胎鼠中均有外观、骨骼和内脏畸形可见。     

混合氨基酸稀土配合物的胚胎毒性研究

在孕鼠“致畸敏感期”分别给予农药混合氨基酸稀土配合物（简称ＭＡＲ）１４２８、７１４、３５７ｍｇ／ｋｇ。１４２８ｍｍ／ｋｍ组胎鼠体重、身长、骨化程度和孕鼠体重增值显著降低，胚胎吸收和胎鼠死亡则增高。提示该剂量ＭＡＲ具有明显胚胎毒性。７１４、３５７ｍｇ／ｋｇ剂量组各项指标与对照组比较则无统计差异。     

镉对孕期、哺乳期大鼠及仔代铁代谢的影响

采用含有正常足量铁（２３０ｍｇ／ｋｇ）和不同剂量镉（０，２５ｍｇ／ｋｇ，８５ｍｇ／ｋｇ）的饲料喂饲妊娠和哺乳大鼠以探讨镉对微量元素铁代谢的可能影响。结果显示，低剂量与高剂量的镉均可导致孕鼠和哺乳大鼠体内多器官和组织中镉的蓄积和铁含量下降，肝、肾受累最甚。胎盘和乳腺似有某种屏障作用阻止镉由母体经胎盘和乳汁侵染子代，各实验组动物乳汁及胎鼠、幼鼠脏器中镉含量极低并无组间差异。但镉对铁代谢的干扰作用引起母体组织中的铁含量下降，对子代动物的铁营养产生极明显的影响，与对照组比较，低镉组和高镉组胎鼠全尸铁含量分别下降了２２．５％和５７．１％，幼鼠肝脏铁含量下降了５８％和６７％，脾脏铁减少了１５％和３７％。     

锰对仔鼠血液,脑及睾丸组织中微量元素的影响

为研究大鼠孕期染锰后对其仔鼠血液、脑及睾丸组织中微量元素的影响,将妊娠雌性大鼠随机分为３组,腹腔注射氯化锰,剂量分别为０、７．５和１５ｍｇ／ｋｇ,测定出生２０天仔鼠的血液、脑及睾丸组织中锰、锌、铜的含量,结果与对照组比较,１５ｍｇ／ｋｇ染锰组脑及睾丸组织中锰含量明显增高（Ｐ〈０．０１,Ｐ〈０．０５）;血清锌含量两实验组均明显降低（Ｐ〈０．０１）,１５ｍｇ／ｋｇ染锰组脑及睾丸组织中锌含量均明显降低（Ｐ〈０．０１）;１５ｍｇ／ｋｇ染锰组脑组织中铜含量明显增高（Ｐ〈０．０５）。说明孕期染锰后通过胎盘和乳汗转运可影响仔鼠体内锰、锌、铜的代谢,从而对仔鼠神经、生殖系统等产生危害。     

砷对小鼠子代生长发育的影响

我们研究了孕鼠接触砷对子代生长发育的影响，结果显示，染砷各组仔鼠机体砷和脑组织砷含量增高，大脑皮层神经细胞结构异常。０．７５ｍｇ／ｋｇ剂量组仔鼠表现为神经行为发育迟缓，外周血淋巴细胞α－醋酸萘酯酶（ＡＮＡＥ）阳性率降低．４．５０ｍｇ／ｋｇ剂量组仔鼠断乳后体重增长缓慢，血液胆碱酯酶活性降低，血清溶血素水平亦显著下降。表明砷可经母体影响胚胎和子代的生长发育。     

甲醛对小鼠胚胎的发育毒性

目的 探讨甲醛对小鼠胚胎的体内发育毒性. 方法随机选择健康性成熟的昆明种小鼠,雌雄介笼产生孕鼠,孕鼠被随机分成5组,每组8只,分别在小鼠妊娠第6～15 d用5、10、20 mg/kg.d的甲醛进行灌胃染毒,每天一次,同时设生理盐水对照和环磷酰胺阳性对照.观察孕鼠的体重增长情况;于妊娠第18 d处死孕鼠取出胚胎,观察胚胎的生长发育状况、死胎和吸收胎鼠数及畸形发生情况. 结果与生理盐水组比较,中、高剂量甲醛染毒可降低孕鼠体重的增长率(P<0.05),高剂量甲醛染毒孕鼠能使胚胎吸收和死亡发生率增加(P<0.05),并可抑制胎盘和胎仔生长发育,中、高剂量甲醛染毒导致胎鼠畸形发生率增加(P<0.05),但对孕鼠和胎仔的毒作用影响均弱于环磷酰胺的毒性作用(P<0.05). 结论甲醛在体内对小鼠胚胎具有发育毒作用和致畸形作用.     

铅对孕鼠生殖内分泌影响的研究

应用放射免疫分析法（ＲＩＡ）和放射配体受体法研究铅对孕鼠生殖内分泌和子宫雌激素受体的影响。ＳＤ雌性大鼠于妊娠第７～１２天，每天灌服１２０ｍｇ／ｋｇ和２２０ｍｇ／ｋｇ硝酸铅水溶液。孕鼠体重、胚胎重量、子宫重量和活胎数与对照组无显著差异。高剂量组孕鼠血清黄体生成激素（ＬＨ）、生乳素（ＰＲＬ）和孕酮（Ｐ）含量明显高于对照组（Ｐ＜０．０１）；染毒组血清促卵泡激素（ＦＳＨ）和雌二醇（Ｅ＿２）含量与对照组无显著差异。染毒组孕鼠子宫Ｅ２受体数与对照组无显著差异，但高剂量组受体亲和力（Ｋａ）明显高于对照组（Ｐ＜０．０１）。孕鼠垂体促性腺激素分泌细胞超微结构无明显病理改变。认为铅可能干扰下丘脑－垂体－卵巢轴的调控机制，导致生殖内分泌功能紊乱。     

镉的性腺和附性腺毒性研究

目的了解镉的雄性生殖毒性机制。方法雄性ＳＤ大鼠皮下注射ＣｄＣｌ２（含镉０．５、１．０和２．０ｍｇ／ｋｇ）染毒，观察镉对性腺和附性腺的影响。结果中、高剂量染镉组的大鼠体重、附睾、前列腺、精囊和睾丸重量均显著低于对照组（Ｐ＜０．０１），且有明显的剂量－效应关系；中、高剂量组的睾丸、附睾、精囊和前列腺的脏器系数分别显著低于对照组和低剂量组（Ｐ＜０．０５）；低剂量组的精子含量和活率显著低于对照组、畸形率显著高于对照组（均Ｐ＜０．０１）；中剂量组的精子含量显著低于低剂量组、畸形率显著高于低剂量组（均Ｐ＜０．０１），且无活精子；高剂量组无精子。结论镉对性腺和附性腺具有明显的毒性。     

孕鼠进食正常和缺锌饲料镉对胎鼠的影响

本文研究镉对胎鼠生长的影响,母鼠饲料缺锌和给镉对胎鼠的影响在时间上的关系。以醋酸镉按1.0,1.5和2.0mg/kg剂量在孕期的不同时间腹腔注入。对照组注生理盐水。标准饲料(包括自来水)和市售缺锌饲料(包括双蒸水)均取样作锌含量测定。缺锌饲养组的     

不同波段红外线对小鼠胚胎发育作用的实验研究

目的:研究不同波段红外线对小鼠胚胎的作用。方法:采用不同波段的红外线对正常孕鼠及环磷酰胺(CP)致毒孕鼠的照射,观察了受孕母鼠的体重变化,活胎率、死胎率、吸收胎率以及胎鼠的身长、尾长、体重等指标。结果:单纯红外线照射各组孕鼠的体重、胎鼠的体重、身长、尾长都有增加。其中中波红外线组与正常对照组相比有显著性差异(P<0.01)。阳性对照组(CP组)与正常对照组比较活胎率、死胎率、吸收胎率、胎鼠的体重、身长、尾长均有显著性的差异(P<0.01),CP可明显抑制胎鼠的发育及降低胎鼠的活胎率。红外线+CP各组与阳性对照组比较,活胎率、吸收胎率、死胎率、胎鼠的体重、身长、尾长均有显著性差异。结论:红外线特别是中波红外线能促进胚胎的生长并对CP引起的胚胎发育障碍有一定的缓解作用。     

锌对低碘孕鼠发育及相关激素影响的研究

目的:观察锌对缺碘孕鼠生长发育及相关激素的影响。方法:应用低碘饲料喂养Wistar雌性大鼠复制缺碘动物模型,同时设补碘、补复合锌和葡萄糖酸锌、补碘加复合锌组。在实验不同时期测尿碘,3个月时将动物模型进行交配,3w内观察孕鼠发育情况,而后处死动物,检查活胎体重、畸胎死胎率和胚胎吸收率,取垂体、甲状腺进行病理学检查,同时检测血清中甲状腺激素、促性腺激素和性激素水平。结果:缺碘组尿碘水平降低,甲状腺肿大,甲状腺激素T4、FT4降低,T3、FT3升高;促性腺激素和性激素异常;缺碘组孕鼠在妊娠期间体重增加缓慢,胎鼠体重降低,死胎、吸收胎增加。补锌组甲状腺重量较缺碘组减轻,甲状腺激素、促性腺激素和性激素部分恢复;胎鼠体重增加,死胎和胚胎吸收率降低。结论:缺碘大鼠补锌可降低甲状腺肿大程度;调节甲状腺激素、促性腺激素和性激素代谢紊乱;拮抗由缺碘所致的孕鼠生殖和胎鼠发育异常。     

不同剂量锌缺乏对小鼠及其胚胎发育的影响

目的 :　用昆明种雌性小鼠建立成不同程度缺锌动物模型 ,研究不同程度锌缺乏和孕早期补锌对小鼠及其胚胎发育的影响 ,并探求其发育毒性作用的阈剂量。方法 :　实验分两阶段进行。实验一用 36只初断乳 1 4～ 1 8g小鼠 ,分为低锌 (ZD)、中锌 (ZM)、常锌 (ZN)三组 ,喂饲含锌分别为 3.0± 0 .5、1 5、30 mg/kg的饲料 ,经 50 d喂养平均体重达 30 g后交配。实验二选用 80只 ,2 5～ 30 g成熟小鼠 ,随机分为低锌组 [ZD,饲料含锌 (3.0± 0 .5) mg/kg];低锌补锌组 (ZS,于孕第 7d将低锌饲料换为含锌 30 mg/kg的常锌饲料 ) ;边缘缺锌组 (MD,饲料含锌 9mg/kg) ;常锌组(ZN,饲料含锌 30 mg/kg)。 2 5d锌耗竭性喂养后交配。所有孕鼠于妊第 1 8d活杀。结果 :　实验一 :低锌组小鼠锌水平显著低于常锌组 (P<0 .0 5) ,有典型缺锌症状 ,几乎全部出现生长抑制 ,58.33%的小鼠衰竭死亡 ,存活小鼠亦不能正常交配妊娠。 1 5mg/kg剂量组小鼠则生长发育良好 ,各项指标与常锌组间无异 (P>0 .0 5)。实验二 :ZD组小鼠血清碱性磷酸酶 (AKP)活性 ,股骨锌含量显著低于 ZN组 (P<0 .0 1 ) ;该组小鼠胚胎有明显发育不良 ,畸胎及死胎出现率显著高于 ZN组 (P<0 .0 1 )。ZS组小鼠在孕第 7d补锌后活胎仔大小已趋正常 (P>0 .0 5) ,畸胎出现率与 ZD?     

Fetal effects of cadmium in pregnant rats on normal and zinc deficient diets

Summary This investigation has shown that not only the extent of fetal resorption and malformation but also the types of malformation seen in rats depend upon the strain used and day of gestation. Furthermore, the effects of zinc deficiency and cadmium administration on the fetus can be at least additive, as was seen for malformations. For fetal resorption, zinc deficiency potentiated the action of cadmium.     

锌缺乏对孕鼠发育及体内促生长有关激素水平的影响

目的　探讨锌缺乏对妊娠大鼠发育及体内促生长有关激素含量的影响。方法　将Wistar妊娠大鼠随机分为缺锌组 (ZD)、对喂组 (PF)、补锌组 (ZS)及正常对照组 (Cont) ,分别给予缺锌 (0 .7mg/ kg)和正常锌 (1 0 0 mg/ kg)饲料喂养 ,观察孕鼠及胎鼠发育情况 ,并采用放射免疫法检测血清中甲状腺素 (T3 、T4 )、促甲状腺素 (TSH)和生长激素 (GH)含量。结果　缺锌组孕鼠在妊娠期间体重没有增加 ;胎鼠出生体重显著低于其他三组 ;血清中激素含量显著低于补锌组和正常对照组。结论　锌缺乏可降低孕鼠血液中促生长有关激素含量 ,导致孕鼠及胎儿生长发育迟缓。     

苯对大鼠的生殖毒性和胚胎发育毒性研究

目的探讨苯对大鼠的生殖毒性和胚胎的体内发育毒性。方法以浓度分别为0、5、10、15mg/m3的苯给雌雄性大鼠静式吸入染毒,观察雄性大鼠精子畸形和雌雄交配受孕情况、受精卵着床数、活胎数、死胎数、吸收胎数及胚胎的生长发育情况。结果苯染毒组大鼠精子畸形率高于空白对照组,随着苯染毒浓度的增加,畸形率有增加(P0.05);与空白对照组比较,中、高剂量苯染毒可抑制胎盘和胎仔生长发育,吸收、死胎发生率增加(P0.05)。结论苯具有雄性生殖毒性,并对胚胎有一定的致畸性作用和发育毒性。     

Teratogenicity study of morpholine salts of fatty acids (oleic acid, 50% water solution) in rats by oral administration

Teratogenicity of morpholine salts of fatty acids was examined in Wistar rats (Crj: Wistar). Morpholine salts of fatty acids (oleic acid, 50% water solution) was given to pregnant rats by gavage once a day from day 6 through day 15 of pregnancy at doses of 0, 234, 468 and 936 mg/kg/day. The pregnant rats were sacrificed on day 20 of pregnancy and their fetuses were examined for malformation. Morpholine salts of fatty acids caused nasal discharge, dirty nose and salivation in pregnant rats at doses from 234 mg/kg/day. However, fetal effects, such as malformation and growth retardation, were not observed even at 936 mg/kg. It was concluded that morpholine salts of fatty acids has no teratogenicity in rats when given by oral administration. The no-observed-adverse-effect level was 936 mg/kg/day for rat fetuses and less than 234 mg/kg/day for pregnant rats.     

不同胎龄大鼠的组织铅分布

为研究不同胎龄胚胎／胎儿的组织铅分布规律,本研究用大鼠作动物模型,观察了４种染毒剂量下不同胎龄大鼠组织中的铅分布。将断乳２周的雌性Ｗｉｓｔａｒ大鼠１２０只,随机分为４组,分别饮含Ｐｂ２＋浓度为０、１０、５０和２００ｍｇ／Ｌ的饮水,１０周后与正常雄鼠交配,将各组孕鼠再随机分为４个亚组,于妊娠第１０、１４、１７、２０天时处死,测孕、胎鼠组织的铅含量。结果胎鼠脑铅含量随胎龄增长而增加,但脑铅浓度保持不变;胎鼠体铅含量随胎龄增长呈增加趋势,但胎龄１０天大鼠的体铅浓度高于１４天者。胎鼠体铅含量于妊娠后期较前期明显增加;胎鼠铅含量随胎龄的增加可能与妊娠后期胎鼠体内不断出现新的铅结合位点,特别是骨骼钙化有关。     

Effects of dietary zinc and cadmium on tissue selenium concentration and glutathione peroxidase activity in rats fed DL-selenomethionine or sodium selenite.

The effects of dietary zinc (Zn) and cadmium (Cd) on tissue selenium (Se) concentration and glutathione peroxidase (GSH-Px) activity were studied in weanling male Wistar rats. One group of rats was fed a purified diet based on casein and sucrose, and the other rats used in a 2 x 2 x 2 factorial arrangement of treatment were fed this diet supplemented with 0.1 mg Se/kg, either as DL-selenomethionine or sodium selenite and plus 100 mg Zn/kg as zinc sulfate or 5 mg Cd/kg as cadmium chloride or both for 4 weeks. Se concentrations in plasma, erythrocytes, muscle, heart, and liver were significantly elevated by Zn. Cd significantly decreased Se concentration in muscle. Addition of Zn to the diets markedly increased (p less than 0.001) hepatic GSH-Px activity. However, Cd in the diets produced a significant increase (p less than 0.001) in erythrocyte GSH-Px activity. These results indicate that Zn level of marginal deficiency (8.6 mg/kg diet) can decrease Se availability and a small excess of Zn increases Se availability for hepatic GSH-Px activity.     

The placental and mammary transport of [14C]menaquinone-4 in rats

The transfer of menaquinone-4 (vitamin K2(20] to the fetus and milk was studied in pregnant and lactating rats, respectively, after oral administration (4 mg/kg) of [3'-14C]menaquinone-4. Intestinal absorption of menaquinone-4 was rapid and the highest level of radioactivity in each tissue except guts of fetal rats was observed at 4h after dosing. The level in the fetal homogenate was low. At that time, the concentration of menaquinone-4 in the fetal liver was 84 ng/g, corresponding to 9% of the value found in the placenta. Therefore, we conclude that the transfer of menaquinone-4 to the developing rat fetus is restricted by the blood-placenta barrier, but that a sufficient amount of menaquinone-4 (more than the essential amount of vitamin K to ensure full carboxylation) can be transferred into the fetal liver. It was also observed that the radioactivity was transferred to milk after oral administration to lactating rats. Milk/blood concentration ratios at 6 and 24h after dosing were 13.8 and 65.1, respectively. The elimination half-life of radioactivity in milk was about 17h. Eighty-four percent of milk of radioactivity was due to menaquinone-4. These results suggest that the prophylactic maternal oral administration of menaquinone-4 may be efficacious for a prophylaxis of neonatal and infantile vitamin K deficiency.